Clostridium septicum Aortitis of the Infrarenal Abdominal Aorta

Clostridium septicum aortitis is a rare infection that has a strong association with occult colonic malignancy. There is also emerging evidence to support the combination of medical and surgical management over medical management alone. To the best of our knowledge, we report the 40th known case of C. septicum aortitis.


Introduction
Clostridium septicum (C. septicum) can cause a wide array of clinical manifestations including gas gangrene. One proposed mechanism of infection is by hematogenous spread from the gastrointestinal tract. Gas gangrene caused by C. septicum is associated with colorectal cancer and other defects of the bowel. Alpern et al and Kornbluth et al have reported an association between C. septicum infection and malignancy [1,2]. We describe a rare case of C. septicum-induced aortitis affecting the infrarenal abdominal aorta. We received consent from the patient for publication of this case.
C. septicum is a Gram-positive, spore forming, obligate, anaerobic bacterium. C. septicum causes myonecrosis through the release of exotoxins such as the alpha toxin [3], lethal toxin, and hemolytic toxin.
An infected aneurysm, also known as a "mycotic aneurysm" or "microbial arteritis", is an aneurysm arising from bacterial infection of the arterial wall. It was described first by Osler in 1887 [4]. This complication is not all that uncommon and it is caused by the hematogenous spread of bacterial infection. Given that the current treatment modalities for aortic aneurysms may be time sensitive, early diagnosis is prudent.
Without medical or surgical management, severe hemorrhage, rupture, or uncontrolled sepsis may occur [5]. Despite this, symptomatology is frequently nonspecific during the early stages so a high index of suspicion is required to make the diagnosis.
We present a case of a 78-year-old patient who was found to have an incidental aortitis in the setting of intussusception and colon cancer.

Case Report
The patient was a 78-year-old male who presented with chronic diarrhea of 2 years' duration. He initially presented to his gastroenterologist who performed a colonoscopy and discovered colonic cancer at the hepatic flexure. Pathology revealed moderately differentiated adenocarcinoma with complex focally cribriform glands formed by cells with enlarged hyperchromatic nuclei. The patient was then admitted to the hospital for further workup and staging of the malignancy.
On admission, the patient had a fever of 39.0 °C, heart rate of 96 beats/min, hemoglobin of 12 mg/dL, and leukocytosis of 17,000/μL. Tumor marker carcinoembryonic antigen was 137 μg/L.
He underwent a CT scan for further malignancy staging and was found to have an intussusception at the location of his newly discovered colonic cancer (Fig. 1).
The CT scan also incidentally revealed findings consistent with aortitis with a periaortic abscess and an asymptomatic pseudoaneurysm in the infrarenal abdominal aorta ( Fig.  2 and 3). Blood cultures also grew C. septicum which was pan-susceptible. On further questioning, the patient endorsed a 10 pound weight loss over the preceding few months with intermittent explosive diarrhea along with decreased appetite, weakness, and generalized malaise. The patient denied other constitutional symptoms such as fever or chills. Prompt resection of the infrarenal aorta was performed. Pre-and postoperatively the patient was started on intravenous aztreonam, vancomycin, and metronidazole and sent home on oral metronidazole. In the interim, he also underwent elective definitive management of his neoplasia with colon resection of the hepatic flexure mass.
The patient was doing well post-operatively for several months undergoing meticulous multi-disciplinary care until he     started developing fevers, chills, and weakness. He presented back to the hospital and was found to have an abscess at the post-operative anastomotic site of the colon cancer resection at the hepatic flexure. Blood cultures were drawn which regrew C. septicum. He was managed with the same combination of intravenous antibiotics and was discharged home on oral metronidazole and levofloxacin. The plan was to continue the current antibiotics and to do a follow-up CT scan to confirm the response of the abscess to the proposed treatment.

Discussion
A typical finding of clostridial mycotic aneurysms in the CT scan is gas formation surrounding the aorta or peripheral arteries. Clostridia can proliferate in tissues when oxidationreduction falls or the pH is reduced, which may occur with arterial injury, necrotic tissue, or anoxic tissue with lactic acid accumulation [6]. For this reason, clostridial infection is frequently associated with gastrointestinal or hematologic malignancy. Kornbluth et al reported an associated malignancy in 81% of patients with C. septicum infection, which has been validated by other similar studies [2]. A study of human fecal flora in healthy volunteers showed that C. septicum is not normally present [7]. Only about 1.3% of clostridial infections are caused by C. septicum [8]. It is believed that ulcerative lesions of the gastrointestinal tract, especially colon carcinoma, can allow clostridial organisms to enter the bloodstream and seed an atherosclerotic focus in the aorta, resulting in the development of mycotic aortic aneurysm [9]. Therefore, the diagnosis of clostridial mycotic aortic aneurysm requires a thorough search for an occult malignancy. Of the total 40 cases of aortitis caused by C. septicum that have been reported and listed in Table 1  , at the time of the review the aneurysm was located in the infrarenal aorta in 13 (34.2%), abdominal aorta (including juxtarenal and suprarenal) in nine (23.6%), the thoracic aorta (ascending part and the aortic arch) in 10 (26.3%), the iliac artery in three, the thoracoabdominal in two, the whole aorta in two, the popliteal artery in one, and the thoracic aorta and abdominal aorta (double aneurysm) in one patient. Of these 40 cases, seven cases experienced aortic dissection and one case experienced aortic rupture. Also, two cases were reported in young age (16 years old and 22 years old) and both of them ended up in aortic dissection and death. In these 40 cases, there were 30 cases (78.9%) with colon neoplasm. Twenty-two of the 24 patients who underwent vascular surgery survived (91.6% survival rate, 8.4% mortality rate), whereas four out of five cases that treated medically only died (80% mortality). Out of these 40 cases, 10 cases died before getting accurate diagnosis, diagnosed at autopsy, or did not make it till the time of the surgical intervention. Surgical treatment seems to be needed to achieve optimal results.
The traditional surgical dictum mandates excision of the infected aneurysm, wide local debridement, administration of antibiotics, and remote grafting in the form of extra-anatomic bypass through a clean surgical field. However, in situ reconstruction has received emphasis in recent years. In the presence of a positive gram stain or purulence, excision of the pseudo aneurysm with an extra-anatomic bypass should be used, followed by a 6-week course, at the minimum, of parenteral antibiotics. In the absence of purulence and with a negative gram stain, in situ graft reconstruction with synthetic material can be utilized, followed by a 6-to 8-week course of organismspecific antibiotics [20].
Our patient had an emergent right axillofemoral bypass with an 8 mm heparin bonded polytetrafluoroethylene (PTFE). Abdominal aortic exploration and ligation of the infrarenal abdominal aorta was performed with aortic debridement. Thrombectomy of the right axillofemoral bypass was also performed and the peripheral perfusion was left intact. As per current treatment guidelines, the patient then received longterm parenteral antibiotics with aztreonam, vancomycin and metronidazole [9]. He was eventually transitioned to only oral metronidazole and continued to clinically improve up until the discontinuation of antibiotics.

Conclusion
Our literature review revealed that surgical and medical management (8.4% mortality rate) was superior to medical management alone (80% mortality rate) in patients with this rare condition which is summarized in Table 2. Consideration of immediate surgical management in addition to medical man- agement of these patients should be given.
Owing to the rare nature of the condition, and most cases being managed with a combination of medical and surgical management, one limitation of our conclusion could be that the number of patients treated only medically might be too small to make a confirmed recommendation of the treatment goals and standards going forward.
In conclusion, our case is one of few reported cases of aortic aneurysm related to clostridium bacteremia. Most of the reported cases in the literature have been associated with colonic malignancy like in our patient. Hence, it would be prudent for clinicians to do a thorough search for malignant processes in patients presenting with similar complaints and C. septicum bacteremia, and also give serious consideration to prompt surgical management of the same.